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Unlike HP1\u03b1 and HP1\u03b2, which localize primarily to heterochromatin, HP1\u03b3 predominantly occupies euchromatin, suggesting a direct role in transcriptional regulation. Here, we identify HP1\u03b3 as a high-risk oncogene in colorectal cancer (CRC). Genome-wide analysis and disease-free survival (DFS) correlation studies revealed that high expression of HP1\u03b3 is associated with poor DFS in CRC patients, and we confirmed HP1\u03b3 upregulation in colon adenocarcinoma (COAD), the predominant CRC subtype. Functional assays demonstrated that HP1\u03b3 overexpression enhances tumor cell proliferation, migration, and colony formation\n                    <jats:italic>in vitro<\/jats:italic>\n                    , while siRNA-mediated knockdown suppressed these phenotypes.\n                    <jats:italic>In vivo<\/jats:italic>\n                    studies showed that HP1\u03b3 drives tumor growth, increasing both volume and weight in xenograft models. Mechanistically, HP1\u03b3, via its chromo shadow domain (CSD), physically interacts with the beta-transducin repeat domain (BTD) of recombination signal binding protein for immunoglobulin kappa J region (RBPJ), the transcriptional factor of the Notch pathway. Intriguingly, RBPJ upregulation counteracts HP1\u03b3-induced hyperproliferation, implicating HP1\u03b3 as a critical modulator of Notch signaling. Our findings establish HP1\u03b3 as a promoter of CRC progression through suppression of Notch pathway components, highlighting its potential as a diagnostic marker or therapeutic target in CRC.\n                  <\/jats:p>","DOI":"10.1007\/s10565-026-10205-z","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T18:53:23Z","timestamp":1782932003000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["HP1\u03b3 promotes the progression of colorectal cancer through interaction with RBPJ of the Notch signaling pathway"],"prefix":"10.1007","volume":"42","author":[{"given":"Rui-Bao","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Jia","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ting","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Ting","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Yi","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Tong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De-Cai","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De-Xin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin-Yun","family":"Che","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Lin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Rui","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Lin","family":"Mo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Yao","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Zhi","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong-Zhi","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-Fei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang-Lin","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Jie","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Quan","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Yang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"issue":"17","key":"10205_CR1","doi-asserted-by":"publisher","first-page":"3593","DOI":"10.1242\/dev.063610","volume":"138","author":"ER Andersson","year":"2011","unstructured":"Andersson ER, Sandberg R, Lendahl U. 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The tissue collection procedure with informed consent was approved by the Clinical Ethics Committee of the Chinese PLA General Hospital. The experimental protocols were evaluated and approved by the animal health and ethics committee of Tsinghua University. This study was implemented in line with the Animal Research: Reporting of\n                      In Vivo\n                      Experiments (ARRIVE).","order":1,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","label":"Conflicts of interest","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"108"}}